Cardiovascular diseases and major cardiovascular events are a leading cause of morbidity and mortality. Such disease and events are caused by abnormalities in haemostasis. Maintenance of normal haemostasis—between bleeding and thrombosis—is subject to complex regulatory mechanisms. Uncontrolled activation of the coagulant system or defective inhibition of the activation processes may cause formation of local thrombi or embolisms in vessels (arteries, veins) or in heart cavities. This may lead to serious thromboembolic disorders, such as myocardial infarct, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transitory ischaemic attacks, peripheral arterial occlusive disorders, pulmonary embolisms or deep venous thromboses.
Cardiovascular diseases and events have traditionally been managed by antiplatelet therapies or anticoagulant therapies. Aspirin is known to reduce platelet aggregation. Specifically, aspirin irreversibly blocks the formation of thromboxane A2, which reduces platelet aggregation. As such, aspirin reduces the risk of secondary ischemic events in individuals who have experienced coronary artery disease (e.g., angina, myocardial infarct, peripheral artery disease, or cerebrovascular ischemia). Aspirin also may reduce the risk of initial thrombotic events in healthy individuals who are at risk of suffering a major cardiovascular event. For this reason, many individuals take aspirin on a regular basis for the primary or secondary prevention of thromboembolic disease.
Unfortunately, aspirin only reduces platelet aggregation by blocking formation of thromboxane A2, and the coagulation cascade is a complex process that is mediated by numerous other factors. Furthermore, the use of aspirin can be accompanied by undesirable side effects including major bleeding events (e.g., gastrointestinal bleeding).
Anticoagulant drugs target various procoagulant factors in the coagulation pathway to reduce the risk of thrombotic disorders by reducing coagulation. One new class of anticoagulant drugs is Factor Xa inhibitors, which play a central role in the cascade of blood coagulation by inhibiting Factor Xa directly.
Rivaroxaban is a Factor Xa inhibitor drug used to treat disorders including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used to help prevent strokes or serious blood clots in people who have atrial fibrillation.
The use of rivaroxaban, however, presents considerable risk to patients. Because rivaroxaban reduces blood clotting, higher than expected blood concentrations of rivaroxaban can cause serious adverse events, most notably elevated rates of internal bleeding/hemorrhage. Conversely, any under dosing of the drug leaves a patient at risk of potentially fatal clotting events.
Because both aspirin and rivaroxaban, separately, present significant bleed risks, the combined use can be dangerous.